Background: Dysregulation of FGFR signaling by FGFR translocations is involved in the pathogenesis of CCA. FGFR2 translocations occur almost exclusively in pts with intrahepatic CCA (iCCA) with an incidence of 13%–15%.1 INCB054828, a selective, potent oral inhibitor of FGFR1, 2, and 3, is being evaluated in a phase 2 study (NCT02924376) of pts with previously treated CCA. Methods: Pts are enrolled into cohort A (FGFR2 translocations), cohort B (other FGF/FGFR genetic alterations [GA]), or cohort C (no FGF/FGFR GAs) and receive oral INCB054828 13.5 mg once daily on a 21‐day cycle (2 weeks on, 1 week off) until disease progression or unacceptable toxicity. The primary endpoint is objective response rate (ORR) per RECIST v1.1 in cohort A based on independent review. Secondary endpoints include ORR in cohorts B and C, progression-free survival (PFS), overall survival, and safety. We report interim efficacy and safety data. Results: At data cutoff (27 Nov 2017) 47, 22, and 18 pts were enrolled in cohorts A, B, and C, respectively. In cohort A, 94% (44/47) had iCCA, 98% (46/47) had ECOG PS ≤ 1, and 60% (28/47) received ≥ 2 prior therapies. Of 45 evaluable pts in cohort A, 8 (18%) had a confirmed partial response (PR; 1/8 with unconfirmed complete response) and 26 (58%) had stable disease (3/26 had unconfirmed PRs); the best ORR was 24% (95% CI, 12%–37%). Median PFS was 6.8 months (95% CI, 3.6–9.2 months). No responses were observed in cohorts B or C; median PFS was 1.4 and 1.5 months, respectively. The most common treatment-emergent adverse events (TEAEs) in all pts (N = 87) were hyperphosphatemia (56%), alopecia (36%), and diarrhea (32%). Hyperphosphatemia was managed with diet, phosphate binders, or dose modification. Most frequent grade 3/4 TEAEs were hyponatremia (8%) and hypophosphatemia (7%). Conclusions: INCB054828 was generally well tolerated and showed preliminary efficacy in pts with previously treated advanced iCCA with FGFR2 translocations. Long-term follow-up data will be presented. 1. Graham RP, et al. Hum Pathol. 2014;45:1630-1638. Clinical trial identification: NCT02924376. Editorial acknowledgement: Medical writing assistance was provided by Michael R. Convente, PhD, of Scientific Pathways, Inc, and funded by Incyte. Legal entity responsible for the study: Incyte Corporation. Funding: Incyte Corporation. Disclosure: A. Hollebecque: Honoraria: Servier, Merck, Serono; Membership on any entity’s Board of directors, advisory committees: Amgen, Gritstone Oncology. M. Borad: Research funding: Incyte Pharmaceuticals. V. Sahai: Consultancy, Honoraria: Halozyme, Celgene, NewLink; Research funding: Bristol-Myers Squibb, Celgene; Membership on any entity's Board of directors, Advisory committees: Celgene, Halozyme. D.V.T. Catenacci: Consultancy (Includes expert testimony): Merck, Bristol-Myers Squibb, Lilly, Five Prime, Genentech/Roche, Amgen, Taiho, Foundation Medicine, Guardant Health; Research funding: Genentech/Roche; Honoraria: Merck, Bristol-Myers Squibb, Lilly, Five Prime, Genentech/Roche, Amgen, Taiho, Foundation Medicine, Guardant Health; Speakers Bureau: Foundation Medicine, Guardant Health, Lilly, Merck, Genentech. A. Murphy: Research funding: Bristol-Myers Squibb. G. Vaccaro: Consultancy (Includes expert testimony): Exelixis; Research funding: Celgene, Merck Sharpe, Dohme, Lilly, Astellas, EMD Serono, Incyte, Bristol-Myers Squibb, Array BioPharma, Newlink Genetics; Honoraria: Bayer. A. Paulson: Equity Ownership: Immunomedics; Membership on any entity’s Board of directors, Advisory committees: Ipsen, Bristol-Myers Squibb, Eisai, Taiho, Merrimack. D-Y. Oh: Research funding: AstraZeneca. L. Féliz, C. Lihou, H. Zhen: Employee, Equity ownership: Incyte. G.K. Abou-Alfa: Consultancy (Includes expert testimony): Agios, Amgen, Antengene, Aptus, Aslan, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Boston Scientific, Carsgen, Celgene, Casi, CytomX, Daiichi, Debio, Delcath, Eisai, Exelixis, Gilead, Halozyme, Inovio, Ipsen, Merck, Onxeo, PCI Biotech, Roche, Sanofi, Servier, Silenseed, Sillajen, Sirtex, Vicus, Yakult; Research funding: Agios, Array, AstraZeneca, Bayer, Bristol-Myers Squibb, Casi, Celgene, Exelixis, Genentech, Incyte, Lilly, Mabvax, Medimmune, Momenta, Novartis, OncoMed Pharmaceuticals, Roche.